Prostate cancer (PCA) is the most common cancer among males of Western countries1A and is a complex heterogeneous disease that acts differently in different men. The real cause of prostate cancer is still unknown. However, androgen and the androgen receptor (AR) are postulated to play crucial roles in the development of prostate cancer.2A The current treatment for prostate cancer is a combination of surgery, radiation, and chemotherapy. Androgen deprivation is a therapy currently in use for both primary and advanced PCA.1 This treatment exerts its effect on target tissue by either blocking androgen [testosterone (T) and dihydrotestosterone (DHT)] synthesis or preventing binding of androgens to the androgen receptor (AR). The consequence of both strategies is interference with androgenic effects responsible for stimulation of prostate cancer cell growth. However, even the highly androgen-dependent cases of PCA that are initially responsive to androgen deprivation therapy eventually develop resistance due to selection or adaptation of androgen-independent clones.2,3 For these patients, no therapy has been shown to be effective4 and new therapeutic strategies are urgently needed.
The therapeutic agents used clinically include steroidal antiandrogens, such as cyproterone acetate, and nonsteroidal antiandrogens, such as flutamide and bicalutamide. The steroidal antiandrogens possess partial agonistic activity and overlapping effects with other hormonal systems, leading to many complications including severe cardiovascular problems, gynecomastia, loss of libido, and erectile dysfunction.3A,4A,5A The nonsteroidal antiandrogens show fewer side effects and have improved oral bioavailability; therefore, they are favored over the steroidal antiandrogens. However, antiandrogen withdrawal syndrome has been discovered in patients receiving nonsteroidal antiandrogens for several months.6A,7A Long-term drug usage probably leads to mutation of the AR, and the nonsteroidal antiandrogens now exhibit agonistic activity to the mutant AR.8A In addition, the clinically available antiandrogens are unable to kill prostate cancer cells, and within one to three years of drug administration, the cancer usually progresses into an androgen refractory phenotype, which is not curable. The poor clinical outcome of advanced metastatic PC highlights the urgent need to develop effective novel agents for prevention and treatment of this disease.
Androgen receptor down-regulating agents (ARDAs) have emerged as an attractive target for the development anti prostate cancer drugs.5,5A,6A,7A,8A Until recently most of the agents known as ARDAs were natural chemicals.11-15 
The androgen receptor (AR) is central to growth signaling in prostate cancer cells and it may be that the AR remains functional and active in androgen-independent/refractory prostate cancer through a variety of mechanisms aimed at increasing the growth response to lower levels of a wide variety of compounds.5-7 In the castrate environment, prostate cancer cells develop a growth advantage by amplifying or mutating the AR, altering AR co-regulatory molecules and developing ligand-independent AR activation pathways.8 Indeed, the AR is expressed in all histological types and stages of PCA, including hormone refractory tumors.9 
Various compounds, hereafter referred to as androgen receptor down-regulating agents (ARDAs), are capable of decreasing the expression and/or function of the AR. Until recently, most of the known ARDAs are dietary compounds (natural products) including, (−)-epicatechin (1), quercetin (2), curcumin (4) and vitamin E succinate (5).11-15 The potential implication of these dietary chemicals (nutraceuticals) on prevention of development and progression of PCA has recently been reviewed by Young et al.16 Other agents, such as flufenamic acid17 (3, a nonsteroidal anti-inflammatory agent) and LAQ82415 (a histone deacetylase inhibitor), have also been shown to decrease AR expression in LNCaP prostate cancer cells. The structures of these compounds are presented in FIG. 1. All five compounds are found to decrease AR protein and mRNA expression. Furthermore, they were shown to decrease AR promoter activities as well. However, studies with these molecules have shown that the mechanism by which they potentiate their effects on the AR is not clear.11-14, 17 Recent studies by Nelson and colleagues19 indicate that the anti-prostate cancer activities of Scutellaria baicalenisis, a botanical with a long history of medicinal use in China, was attributed to four compounds that function in part through the inhibition of the AR signaling pathway. Interestingly, the four active compounds from this plant share the same flavone scaffold as that of epicatechin and quercetin. In addition, curcumin continues to be used as a lead compound to design and synthesize analogs as potential antiandrogenic agents for the treatment of prostate cancer.20-23 
Therefore, it would be desirable to provide new drugs that lead to inhibition of the Androgen synthesis and AR down-regulation and/or AR modulation, which may be useful for preventing the development, progression and treatment of various cancers, such as, for example, prostate cancer. Further, it would be desirable to provide a novel and effective strategy for identifying these types of new drugs.